Longitudinal study of tumor‐associated macrophages during tumor expansion using MRI

Abstract

MRI is being used increasingly for the noninvasive longitudinal monitoring of cellular processes in various pathophysiological conditions. Macrophages are the main stromal cells in neoplasms and have been suggested to be the major cell type ingesting superparamagnetic iron oxide (SPIO) nanoparticles. However, no MRI study has described longitudinally the presence of tumor-associated macrophages (TAMs) during tumorigenesis with histological confirmation. To address this, we injected SPIO nanoparticles into the circulation of tumor-bearing mice and used MRI and post-mortem histology to monitor TAMs at different time points. The MRI results demonstrated that TAMs, as hypointense signals, appeared continually with the expansion of the tumor. The histological findings also revealed that SPIO-labeled TAMs tended to deposit closer to the vessel lumen with time prior to rapid tumor growth. The present study demonstrates the potential of using MRI to assess longitudinally TAM accumulation during tumorigenesis, and provides the first in vivo insight into the topographical arrangement of TAMs in relation to the progression of tumors. In vivo monitoring of the presence of TAMs could be useful for the development of tumor treatments that target TAM functions.

EBV Oncogene N-LMP1 Induces CD4 T Cell–Mediated Angiogenic Blockade in the Murine Tumor Model

“…It has been demonstrated that the recruitment of these cells into the tumor microenvironment is crucial for de novo vessel formation and angiogenic switch (43). Consistent with this idea, we also observed early stepwise deposits of myeloid cells close to the vessel lumen (44), and the timeline of deposition matches the timeline of the multiple high K trans peaks developing from day 7 to day 14 ( Fig. 1).…”

A novel probe for the non-invasive detection of tumor-associated inflammation

“…A mix of microscopic (cellular resolution) and whole-animal imaging methods were used to investigate the distribution of the reagent, 41 , 42 the route of accumulation at the tumor site, 43 and examples of the complex interplay between host and tumor cells 44 , 45 . The optical imaging of an unrelated, integrin-targeting PFC-NIR formulation has previously been used to study tumor vasculature 46 .…”

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid

“…In-vivo labeling of monocytes/macrophages with iron-oxide particles for MRI has been applied to image many disease conditions, such as graft rejection, atherosclerotic plaques, tumors, abdominal aortic aneurysm, renal ischemia, and Alzheimer’s disease [2,10,25,27,28,29,30,31,32,33]. Our laboratory has been able to monitor the infiltration of macrophages labeled with USPIO or MPIO particles at rejecting kidneys, hearts, and lungs in our rat models for organ transplantation using the in-vivo labeling procedure [2,10,25,53,54].…”

“…Non-invasive in-vivo MRI of monocytes/macrophages labeled with iron-oxide particles may lead to a better understanding of the pathogenesis of many diseases, including graft rejection [2,10,25,26], atherosclerotic plaques [27,28], tumors [29,30], abdominal aortic aneurysm [31], renal ischemia [32], Alzheimer’s disease [33], etc. Due to the fact that monocytes/macrophages are phagocytes, they can be labeled in vivo by a direct injection of suitable iron-oxide particles.…”